Tumors are dependent upon new blood vessel formation, or angiogenesis, for expansive growth. Our recent analysis of gene expression led to the identification of several genes in endothelial cells that line tumor blood vessels including GPR116, CD137 and CD276. The products of these genes are of particular interest because they reside on the cell surface and may therefore be directly accessible to blood-borne therapeutics. In an attempt to understand their functional role in angiogenesis, we have begun to generate conditional knockouts for GPR116, CD137 and CD276. Because these genes are also likely to be involved developmental angiogenesis we are generating conditional floxed alleles using cre/flp technology such that the gene can be disrupted specifically in the vessels of adult tissues. By challenging gene disrupted mice with tumors, we hope to determine if any of these genes are critical for tumor angiogenesis. The studies should also allow us to better understand the normal physiological function of these genes.